Following viral infections, the first line of defense consists of a highly organized and aggressive innate immune response, while the adaptive immune response, lagging behind, only develops in the context of an active innate immunity. While we have gained extensive knowledge regarding the mechanisms that determine the specificity of the adaptive immune response, very little is known about the mechanisms that determine the recognition of HIV-1 by the innate immune response. However, not only is the innate immune response critical in viral containment at a time when the adaptive immune response is just developing, it is also critical in shaping the function of the subsequent adaptive immune response. Therefore comprehensive studies aimed at deconstructing this early critical arm of the immune response, and its relationship to the adaptive immune response, are necessary to begin to more globally understand the correlates of protective immunity. Since the initial description of pattern recognition receptors, including Toll-like Receptors (TLRs), it has become more and more apparent that these receptors play a crucial role in